1. Field of the Art
The present invention relates to a diagnostic agent useful for diagnosis of heart disease such as myocardial infarction and myocardial disease by imaging, and a method for the diagnosis of heart disease with use of the diagnostic agent.
In recent years, in the diagnosis of heart disease such as myocardial infarction, diagnosis by imaging which involves administering a radiolabeled tracers into a body, detecting .gamma.-rays emitted by the radioisotope to convert the same into an image, processing the image with a computer to obtain a two- or three-dimensional image, and diagnosing the site or size of the myocardial infarction on the basis of the image thus obtained has made rapid progress. However, tracers used heretofore in the diagnosis by imaging in cardiac nuclear medicine have not always been able to depict specifically the site of myocardial infarction.
For example, T1 scintigraphy of myocardium using thallium-201 (.sup.201 T1) applies the mechanism wherein the T1 behaves in vivo similarly as potassium ion and is taken into cells of the heart liver, kidneys, endocrine organs, tumors and the like where turnover rate is relatively fast, whereby normal cardiac muscle is depicted while the T1 is not ingested into necrotized or ischemic cardiac muscle at an infarction site, which site is depicted as a defect. Accordingly, the T1 does not always depict cardiac muscle specifically, and it has also been difficult to determine by this method whether the infarction occurred recently or in the past.
Pyrophosphate scintigraphy of myocardium, on the other hand, utilizes the phenomenon of technetium -99m(.sup.99m Tc)-labeled pyrophosphate accumulating at an infraction site, which site is depicted as a positive scintigram. This tracer, however, deposits also in the peripheral region of the infarction site and thus is liable to overestimate the infarction area.
2. Prior Art
As a method intended to overcome the above described problems accompanying the conventional tracers, a method using a radiolabeled antibody for cardiac myosin has recently attracted considerable attention. In this method use is made of an antibody obtained by purifying anti-serum prepared by immunizing animals with purified cardiac myosin or its active fragment such as (Fab').sub.2 fragment obtained by treating the antibody with pepsine, both the antibody and its active fragment being radiolabeled and reported to accumulate densely at an infarction site. (cf. U.S. Pat. No. 4,036,945)
However, a myosin molecule has a sub-unit structure comprising two heavy chains and four light chains (two species in the case of human cardiac muscle), so that the anti-serum obtained by immunization with the myosin, even if purified by means of affinity chromatography, also contains antibody molecules specific for light chains. In myocardial infarction, myocardial cell membranes in a necrotized region are destroyed whereby cardiac myosin light chains are released into the blood together with polypeptides such as creatine phosphokinase (CPK) and lactate dehydrogenase. Thus, the antibody having specificity to myosin light chain and its active fragment form an immune complex with the light chain released into the blood and are consumed on the route to the infarction site. Meanwhile, there is the possibility of the immune complex inducing an allergic reaction and various other biological reactions. A further problem is that the anti-serum can be prepared only in a limited quantity and therefore cannot be supplied in a large quantity for clinical purposes.